Document Detail


Pravastatin induces placental growth factor (PGF) and ameliorates preeclampsia in a mouse model.
MedLine Citation:
PMID:  21187414     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Preeclampsia is a relatively common pregnancy-related disorder. Both maternal and fetal lives will be endangered if it proceeds unabated. Recently, the placenta-derived anti-angiogenic factors, such as soluble fms-like tyrosine kinase-1 (sFLT1) and soluble endoglin (sENG), have attracted attention in the progression of preeclampsia. Here, we established a unique experimental model to test the role of sFLT1 in preeclampsia using a lentiviral vector-mediated placenta-specific expression system. The model mice showed hypertension and proteinuria during pregnancy, and the symptoms regressed after parturition. Intrauterine growth restriction was also observed. We further showed that pravastatin induced the VEGF-like angiogenic factor placental growth factor (PGF) and ameliorated the symptoms. We conclude that our experimental preeclamptic murine model phenocopies the human case, and the model identifies low-dose statins and PGF as candidates for preeclampsia treatment.
Authors:
Keiichi Kumasawa; Masahito Ikawa; Hiroyasu Kidoya; Hidetoshi Hasuwa; Tomoko Saito-Fujita; Yuka Morioka; Nobuyuki Takakura; Tadashi Kimura; Masaru Okabe
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-12-27
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  108     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-26     Completed Date:  2011-04-26     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1451-5     Citation Subset:  IM    
Affiliation:
Department of Experimental Genome Research, Research Institute for Microbial Diseases, Osaka University, Suita 565-0871, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Animals, Newborn
Cell Line
Disease Models, Animal*
Female
HEK293 Cells
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage,  pharmacology
Injections, Intraperitoneal
Lentivirus / genetics
Male
Mice
Mice, Transgenic
Placenta / metabolism
Pravastatin / administration & dosage,  pharmacology*
Pre-Eclampsia / genetics,  metabolism,  prevention & control*
Pregnancy
Pregnancy Proteins / genetics,  metabolism*
Transduction, Genetic
Vascular Endothelial Growth Factor Receptor-1 / genetics,  metabolism
Chemical
Reg. No./Substance:
0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 0/Pregnancy Proteins; 144589-93-5/placenta growth factor; 81093-37-0/Pravastatin; EC 2.7.10.1/FLT1 protein, human; EC 2.7.10.1/Vascular Endothelial Growth Factor Receptor-1
Comments/Corrections
Comment In:
Proc Natl Acad Sci U S A. 2011 Jan 25;108(4):1197-8   [PMID:  21233419 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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